PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV

Poster Allergologie und Immunologie
P 5
Alterations in the regulatory T cell population in atopic dermatitis-like cutaneous
inflammation in mice.
Verena Martinz 1
Christoph H. Tripp 1
Daniela Finke 2
Robert Gruber 1
Christine Heufler-Tiefenthaler 1
Matthias Schmuth 1
Sandrine Dubrac 1
1 Department of Dermatology and Venereology, Innsbruck Medical University,
Innsbruck, Austria
2 Developmental Immunology, Department of Biomedicine, University of Basel, Basel,
Switzerland
Although a role of abnormal immune reactivity in the multifactorial pathogenesis of
atopic dermatitis (AD) is widely accepted, the complex immunological network leading
to AD remains unclear. We characterized the regulatory T cell (Treg) population in AD
patients and in two mouse models of AD exhibiting high epidermal TSLP expression;
i.e., mice topically treated with vitamin D3 (VitD3) or those overexpressing TSLP under
the K14 promotor. Adult patients with AD lesions showed elevated circulating Tregs as
measured by demethylation of CpG dinucleotides in a conserved region of FoxP3 intron
1. Similarly, mice from both mouse models exhibited higher percentages and numbers
of ICOS-expressing CD4+ CD25+ FoxP3+ Tregs in skin draining lymph nodes (sdLN).
Moreover, numbers of natural Tregs were increased. Direct upregulation of Tregs by
VitD3 was excluded by removal of application site. Depletion of Langerin-expressing
dendtitic cells (DC) indicated that other skin- and non-skin-derived DC can induce Tregs
in our mouse models of AD. Furthermore, Tregs from VitD3-treated mice expressed
increased levels of CTLA-4 and GARP and larger amounts of IL-10 and IL-13, if compared
to K14-TSLP transgenic mice. Thus, although we observed increased numbers of
activated Tregs, they are unable to counteract the ongoing skin Th2-inflammation. In
addition, we showed that these Tregs can be induced by all DC subsets.
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